Xylitol is prothrombotic and associated with cardiovascular risk
- PMID: 38842092
- DOI: 10.1093/eurheartj/ehae244
Xylitol is prothrombotic and associated with cardiovascular risk
Abstract
Background and aims: The pathways and metabolites that contribute to residual cardiovascular disease risks are unclear. Low-calorie sweeteners are widely used sugar substitutes in processed foods with presumed health benefits. Many low-calorie sweeteners are sugar alcohols that also are produced endogenously, albeit at levels over 1000-fold lower than observed following consumption as a sugar substitute.
Methods: Untargeted metabolomics studies were performed on overnight fasting plasma samples in a discovery cohort (n = 1157) of sequential stable subjects undergoing elective diagnostic cardiac evaluations; subsequent stable isotope dilution liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses were performed on an independent, non-overlapping validation cohort (n = 2149). Complementary isolated human platelet, platelet-rich plasma, whole blood, and animal model studies examined the effect of xylitol on platelet responsiveness and thrombus formation in vivo. Finally, an intervention study was performed to assess the effects of xylitol consumption on platelet function in healthy volunteers (n = 10).
Results: In initial untargeted metabolomics studies (discovery cohort), circulating levels of a polyol tentatively assigned as xylitol were associated with incident (3-year) major adverse cardiovascular event (MACE) risk. Subsequent stable isotope dilution LC-MS/MS analyses (validation cohort) specific for xylitol (and not its structural isomers) confirmed its association with incident MACE risk [third vs. first tertile adjusted hazard ratio (95% confidence interval), 1.57 (1.12-2.21), P < .01]. Complementary mechanistic studies showed xylitol-enhanced multiple indices of platelet reactivity and in vivo thrombosis formation at levels observed in fasting plasma. In interventional studies, consumption of a xylitol-sweetened drink markedly raised plasma levels and enhanced multiple functional measures of platelet responsiveness in all subjects.
Conclusions: Xylitol is associated with incident MACE risk. Moreover, xylitol both enhanced platelet reactivity and thrombosis potential in vivo. Further studies examining the cardiovascular safety of xylitol are warranted.
Keywords: Artificial sweetener; Cardiovascular disease; Heart attack; Low-calorie sweetener; Nutrition; Platelet; Polyol; Stroke; Sugar alcohol; Thrombosis.
© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected].
Similar articles
-
The artificial sweetener erythritol and cardiovascular event risk.Nat Med. 2023 Mar;29(3):710-718. doi: 10.1038/s41591-023-02223-9. Epub 2023 Feb 27. Nat Med. 2023. PMID: 36849732 Free PMC article.
-
Beverage Consumption and Growth, Size, Body Composition, and Risk of Overweight and Obesity: A Systematic Review [Internet].Alexandria (VA): USDA Nutrition Evidence Systematic Review; 2020 Jul. Alexandria (VA): USDA Nutrition Evidence Systematic Review; 2020 Jul. PMID: 35349233 Free Books & Documents. Review.
-
Vascular endothelial tissue factor contributes to trimethylamine N-oxide-enhanced arterial thrombosis.Cardiovasc Res. 2022 Jul 27;118(10):2367-2384. doi: 10.1093/cvr/cvab263. Cardiovasc Res. 2022. PMID: 34352109 Free PMC article.
-
Health benefits of xylitol.Appl Microbiol Biotechnol. 2020 Sep;104(17):7225-7237. doi: 10.1007/s00253-020-10708-7. Epub 2020 Jul 7. Appl Microbiol Biotechnol. 2020. PMID: 32638045 Review.
-
Untargeted metabolomics identifies trimethyllysine, a TMAO-producing nutrient precursor, as a predictor of incident cardiovascular disease risk.JCI Insight. 2018 Mar 22;3(6):e99096. doi: 10.1172/jci.insight.99096. JCI Insight. 2018. PMID: 29563342 Free PMC article.
Grants and funding
LinkOut - more resources
Full Text Sources